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    Adult Hodgkin Lymphoma Treatment (PDQ®): Treatment - Health Professional Information [NCI] - Early Unfavorable Hodgkin Lymphoma

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    With a 64-month median follow-up, in a preliminary report in abstract form, no differences were observed in event-free survival (89%-92%; P = .38) or OS (91%-96%; P = .98).[15][Level of evidence: 1iiA]

    In summary, these randomized trials support the use of ABVD for four cycles with 20 Gy to 30 Gy IF-XRT. Could the radiation therapy be omitted to minimize late morbidity and mortality from secondary solid tumors and from cardiovascular disease?[16] The NCIC study is the only trial to address this question in patients with early unfavorable HL; although four to six cycles of ABVD alone has improved OS compared with a combined modality approach, the use of EF-XRT in the combined modality arm is excessive by current standards, and late effects will be magnified with these larger fields.[7] In addition, chemotherapy alone was 8% worse in freedom-from-progression compared to the combined modality approach.

    How can we balance an improvement in freedom-from-progression using radiation therapy with chemotherapy against late morbidity and mortality from late effects?[16,17] Randomized studies with or without IF-XRT would be required, but no such studies are currently under way.[16] An indirect comparison for using ABVD alone is that the 94% OS seen for early unfavorable patients in the NCIC study [7] at 11 years is equivalent to the survival seen in the GHSG's HD6 [NCT00002561], HD10 [NCT01399931], and HD11 trials using combined modality therapy at 11 years.[18] A Cochrane meta-analysis of 1,245 patients in five randomized, clinical trials suggested improved survival for combined modality therapy versus chemotherapy alone (HR, 0.40; 95% CI, 0.27-0.61).[19] However, the NCIC study does demonstrate a 92% OS for ABVD alone at a median follow-up of 11.3 years. This would support the use of ABVD for patients with early unfavorable disease. Long-term follow-up, which would account for late toxicities and deaths from combined modality therapy, will not be forthcoming from these trials.[19]

    Patients with bulky disease (≥10 cm) or massive mediastinal involvement were excluded from most of the aforementioned trials. Based on historical comparisons to chemotherapy or radiation therapy alone, these patients currently receive combined modality therapy.[20,21][Level of evidence: 3iiiDiii]

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